A 3D Printed Device for Low Cost Neural Stimulation in Mice

Abstract

Electrical stimulation of the brain through the implantation of electrodes is an effective treatment for certain diseases and the focus of a large body of research investigating new cell mechanisms, neurological phenomena, and treatments. Electrode devices developed for stimulation in rodents vary widely in size, cost, and functionality, with the majority of recent studies presenting complex, multi-functional designs. While some experiments require these added features, others are in greater need of reliable, low cost, and readily available devices that will allow surgeries to be scheduled and completed without delay. In this work, we utilize 3D printing and common electrical hardware to produce an effective 2-channel stimulation device that meets these requirements. Our stimulation electrode has not failed in over 60 consecutive surgeries, costs less than $1 USD, and can be assembled in less than 20 min. 3D printing minimizes the amount of material used in manufacturing the device and enables one to match the curvature of the connector’s base with the curvature of the mouse skull, producing an ultra-lightweight, low size device with improved adhesion to the mouse skull. The range of the stimulation parameters used with the proposed device was: pulse amplitude 1–200 μA, pulse duration 50–500 μs and pulse frequency 1–285 Hz.

Electric Field ApplicationIn VivoRegulates Neural Precursor Cell Behavior in the Adult Mammalian Forebrain

“…The proportion of Iba11 cells (25.9 6 2.6% vs 29.4 6 1.9% Iba11 cells, stim-on and stim-off, respectively) was unaffected (p = 0.3), as was the proportion of proliferating microglia (Iba11 EdU1; 12.7 6 1.8% vs 11.3 6 1.8% Iba11EdU1 cells, stim-on and stim-off, respectively; p = 0.6; Fig. 3H) similar to previous findings (Morrison et al, 2019;Iwasa et al, 2019). Taken together, Figure 2 In vitro electrical stimulation increases cell number and regulates NPC differentiation.…”

“…The 3D-printed electrode base was designed in SOLIDWORKS 2017, and electrodes were prepared as described (Morrison et al, 2019). The cortical stimulating electrodes were made with 127-mm diameter platinum wire and were 2 mm long and 2 mm apart.…”

“…Mice were anesthetized with 1.5-2.5% isoflurane, and the implanted electrode was interfaced with biphasic electrical stimulator (Popovic and Keller, 2005;Morshead et al, 2018) with pulse parameters: ,200 mA, with a ;500-mV cathodal pulse amplitude and a ;125-mV anodal pulse amplitude, at 500-and 2000-ms pulse widths, respectively, followed by a 1000-ms resting phase (Morrison et al, 2019;Iwasa et al, 2019) for a total time of 1 h. Following stimulation, mice were returned to their cages and killed 1 or 3 d later. For tissue analysis, mice were transcardially perfused with ice-cold PBS followed by 4% PFA for tissue analysis, or cervically dislocated and processed for the neurosphere assay as described Neurosphere assay section.…”

“…In the next series of experiments, we asked whether in vivo electrical stimulation had similar effects on endogenous NPCs in the periventricular region of the adult forebrain. Stimulating electrodes were implanted into the cortex with the cathode placed near the midline and the anode placed laterally, as previously reported (Morrison et al, 2019;Iwasa et al, 2019;Fig. 3A).…”

Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in the Presence of Endogenous Electric Fields in Mouse Brains

“…Interestingly, we observed a small but significant increase in cathodally (medially) directed migration of transplanted NPCs with cortical stimulation. Similar to our previous report (Morrison et al, 2019), the charge-balanced biphasic monopolar stimulation did not result in enhanced inflammation as measured by microglia/macrophage number. Overall, our findings reveal cell migration patterns in response to endogenous and applied electrical stimulation, highlighting the potential impact of EFs in modifying cell behavior in vivo.…”